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ABIM Internal Medicine

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12.5 Dermatologic Emergencies & Severe Cutaneous Adverse Reactions

Key Takeaways

  • Dermatologic emergencies is a separately enumerated blueprint subsection under Dermatology.
  • Stevens-Johnson syndrome and toxic epidermal necrolysis are separated by the percentage of body surface with epidermal detachment.
  • Immediate withdrawal of the culprit drug and transfer to a burn or specialized unit are the interventions with the clearest survival benefit in toxic epidermal necrolysis.
  • Drug reaction with eosinophilia and systemic symptoms typically begins two to eight weeks after drug exposure with fever, facial edema, eosinophilia and organ involvement.
  • Mucosal involvement, skin tenderness, a positive Nikolsky sign, fever and lymphadenopathy are the features that separate a severe reaction from a simple morbilliform eruption.
Last updated: August 2026

1. Dermatologic Emergencies & Severe Cutaneous Adverse Reactions (SCAR)

Stevens-Johnson Syndrome (SJS) & Toxic Epidermal Necrolysis (TEN)

  • Pathophysiology: A life-threatening, cell-mediated cytotoxic immune reaction culminating in massive, full-thickness keratinocyte apoptosis and extensive dermoepidermal sheet detachment. Mediated by cytotoxic CD8+ T lymphocytes and natural killer (NK) cells releasing granulysin, perforin, granzyme B, and Fas / Fas-Ligand (FasL) interactions.
  • High-Risk Culprit Medications (SATANE Mnemonic):
    • S — Sulfonamides: Trimethoprim-sulfamethoxazole (TMP-SMX), sulfadiazine, sulfasalazine.
    • A — Allopurinol: Especially in renal impairment or rapid dose titration.
    • T — Tetracyclines / Antiretrovirals: Nevirapine, efavirenz.
    • A — Anticonvulsants (Aromatic): Carbamazepine, Lamotrigine, Phenytoin, Phenobarbital.
    • N — NSAIDs: Oxicam derivatives (Piroxicam, Meloxicam).
    • E — Extras (Antibiotics): Beta-lactams, Cephalosporins, Fluoroquinolones.
  • Pharmacogenomic Risk Alleles:
    • HLA-B*15:02: Strongly associated with Carbamazepine-induced SJS/TEN in individuals of Asian ancestry (Han Chinese, Thai, Malaysian, Filipino). Mandatory FDA genetic screening prior to carbamazepine initiation.
    • HLA-B*58:01: Strongly associated with Allopurinol-induced SJS/TEN and DRESS in Han Chinese, Korean, Thai, and African-American ancestry.
    • HLA-B*57:01: Strongly associated with Abacavir hypersensitivity.
  • Clinical Presentation & Course:
    • Latency: 1 to 3 weeks (7-21 days) after drug initiation.
    • Prodrome: 1-3 days of fever, malaise, sore throat, cough, photophobia, and cutaneous tenderness.
    • Cutaneous Eruption: Rapidly spreading, dusky erythematous and purpuric macules with atypical targetoid lesions (2 concentric zones) that coalesce into flaccid blisters and extensive sheets of denuded skin. Positive Nikolsky sign (epidermal detachment induced by lateral frictional pressure) and Positive Asboe-Hansen sign.
    • Severe Mucosal Involvement (>90% of cases, >=2 distinct mucosal surfaces):
      • Eyes: Severe pseudomembranous conjunctivitis, corneal ulcerations, symblepharon (cicatricial adhesions of eyelids to globe), risk of permanent blindness.
      • Oral/Labial: Painful stomatitis, extensive sloughing, hemorrhagic vermilion crusting.
      • Genitourinary: Urethral/vaginal erosions, vulvar synechiae, urinary retention.
      • Respiratory: Tracheobronchial epithelial detachment causing acute respiratory distress syndrome (ARDS).
  • Classification by Body Surface Area (BSA) of Epidermal Detachment:
    • SJS: < 10% BSA epidermal detachment.
    • SJS / TEN Overlap: 10% to 30% BSA epidermal detachment.
    • TEN: > 30% BSA epidermal detachment (often >50-80%).
  • SCORTEN Prognostic Scoring System (Evaluated within first 24 hours):
SCORTEN Parameter (1 point each)Clinical ThresholdMortality Rate by Total Score
1. Age>= 40 years0 to 1 point: ~3.2% mortality
2. Associated MalignancyYes (hematologic or solid tumor)2 points: ~12.1% mortality
3. TachycardiaHeart Rate >= 120 beats/min3 points: ~35.3% mortality
4. Initial Epidermal Detachment> 10% BSA at day 14 points: ~58.3% mortality
5. Serum Urea Nitrogen (BUN)> 28 mg/dL (>10 mmol/L)>= 5 points: ~90.0% mortality
6. Serum Glucose> 252 mg/dL (>14 mmol/L)—
7. Serum Bicarbonate (HCO3-)< 20 mEq/L (<20 mmol/L)—
  • Emergency Management Protocol:
    1. Immediate Withdrawal of ALL Offending and Non-Essential Medications: Single most critical action affecting survival; each day of delay increases mortality.
    2. Immediate Triage & Transfer to an Accredited Burn Center or Intensive Care Unit (ICU): Specialized nursing, thermoregulation (room temp 30-32°C), and infection control.
    3. Supportive Resuscitation: IV fluid resuscitation with balanced crystalloids titrated to urine output (target 0.5-1.0 mL/kg/h; requires ~25-30% less volume than equivalent thermal burns to avoid pulmonary edema). Enteral nutrition via soft nasogastric tube.
    4. Wound Care: Sterile handling, bland non-adherent dressings (silicone dressings, petrolatum gauze); DO NOT surgically debride non-detached necrotic epidermis (detached skin serves as a biological dressing).
    5. Infection Control: Daily surveillance cultures; NO prophylactic systemic antibiotics (increases selective pressure for resistant Pseudomonas and fungal sepsis); treat only documented infections.
    6. Urgent Ophthalmology Consultation: Aggressive preservative-free lubrication, topical antibiotics, lysis of symblepharon adhesions, and early Amniotic Membrane Transplantation (AMT) within the first 5-7 days to prevent cicatrization and permanent blindness.
    7. Immunomodulatory Therapies: Cyclosporine A (3-5 mg/kg/day IV/PO for 10-14 days; halts apoptosis and improves survival in meta-analyses), Etanercept (anti-TNF; 50 mg SC), or IVIG (2-3 g/kg). High-dose systemic steroids remain controversial due to sepsis risks.

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS / DIHS)

  • Pathophysiology: A severe, life-threatening delayed-type hypersensitivity reaction (Type IVb/IVc) driven by drug-specific T-cell activation in synergy with the reactivation of latent human herpesviruses, predominantly Human Herpesvirus 6 (HHV-6), HHV-7, Epstein-Barr Virus (EBV), and Cytomegalovirus (CMV).
  • High-Risk Culprit Drugs: Allopurinol, Aromatic Anticonvulsants (Carbamazepine, Phenytoin, Lamotrigine), Sulfonamides, Vancomycin, Minocycline, and Dapsone.
  • Characteristic Timeline: Prolonged, delayed latency of 2 to 8 WEEKS (average 3-4 weeks) between drug initiation and symptom onset (distinguishing DRESS from simple morbilliform drug exanthems [1-2 weeks] or SJS/TEN).
  • Clinical Triad & Organ Manifestations:
    1. High Prolonged Fever (>=38.5°C): Present in >90% of patients.
    2. Extensive Cutaneous Eruption: Confluent morbilliform, indurated maculopapular eruption covering >50% BSA, with marked facial edema and periorbital swelling (>70-80% of cases; key diagnostic hallmark) and tender generalized lymphadenopathy.
    3. Multisystem Internal Organ Failure:
      • Liver (70-90%): Severe acute hepatitis with marked transaminitis (ALT/AST >5x ULN), cholestasis, or fulminant hepatic failure.
      • Kidney (10-30%): Acute interstitial nephritis (AIN) with elevated creatinine, proteinuria, and eosinophiluria (classically associated with Allopurinol).
      • Lungs (10-15%): Interstitial pneumonitis, dry cough, hypoxemia.
      • Heart (2-5%): Acute Eosinophilic or Delayed Hypersensitivity Myocarditis (can emerge weeks after rash resolution; presents with cardiogenic shock, arrhythmias, or sudden death; requires troponin and echocardiogram screening).
  • Laboratory Hallmarks:
    • Marked Peripheral Eosinophilia (>= 700 to 1,500/mcL or > 10% total WBC count; present in >90%).
    • Atypical Lymphocytosis (mononucleosis-like reactive Downey lymphocytes).
    • Quantitative PCR detection of circulating HHV-6 DNA.
  • Management & Monitoring:
    • Immediate cessation of the offending medication.
    • Systemic Corticosteroids: Oral Prednisone 0.5 to 1.0 mg/kg/day (or IV Methylprednisolone for severe organ dysfunction).
    • CRITICAL MANAGEMENT RULE: Corticosteroids must be tapered very slowly over 2 to 3 MONTHS (8 to 12 weeks). Rapid steroid tapering triggers severe, fatal disease rebound and recurrent hepatitis.
    • Long-Term Monitoring: Screen for delayed autoimmune sequelae (Autoimmune Thyroiditis [Hashimoto's or Graves'], Type 1 Diabetes Mellitus, Vitiligo, Systemic Lupus) occurring 6 to 12 months after resolution.

Acute Generalized Exanthematous Pustulosis (AGEP)

  • Pathophysiology: T-cell mediated hypersensitivity (Type IVd) where drug-specific CD4+/CD8+ T cells produce massive quantities of Interleukin-8 (CXCL8), orchestrating rapid, massive neutrophilic recruitment into the subcorneal epidermis.
  • Culprit Medications: Beta-lactam antibiotics (Aminopenicillins, Cephalosporins), Macrolides, Quinolones, Hydroxychloroquine, and Diltiazem.
  • Clinical Presentation:
    • Ultra-rapid onset: Erupts within 24 to 48 HOURS (1-2 days) of drug ingestion.
    • High fever (>=38°C) and sudden emergence of dozens to hundreds of tiny (1-2 mm), non-follicular, sterile pinpoint pustules arising on a background of diffuse, edematous erythema. Typically begins in flexural/intertriginous skin folds (axillae, groin, neck) and rapidly disseminates.
    • Labs: Marked leukocytosis with profound neutrophilia (ANC >7,000 to 10,000/mcL); eosinophilia in <30%.
  • Clinical Course & Management: Self-limiting benign course. Discontinue the offending antibiotic. Pustules spontaneously desquamate with a characteristic "collarette" pinpoint peeling within 7 to 14 days. Managed supportively with bland emollients and cool compresses; systemic corticosteroids are rarely necessary.
Test Your Knowledge

A 48-year-old woman with chronic gout was started on Allopurinol 300 mg daily 2 weeks ago. She presents to the emergency department with high fever (39.2°C / 102.6°F), severe malaise, stinging eye pain, and excruciating skin soreness. Physical examination reveals confluent dusky purpuric macules with flaccid bullae covering 35% of her total body surface area. Gentle lateral sliding pressure on normal-appearing skin causes the epidermis to slough off (positive Nikolsky sign). Both eyes show severe conjunctival injection with pseudomembrane formation, and her oral mucosa has extensive painful hemorrhagic crusts. What is the most critical immediate management strategy?

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Test Your Knowledge

A 36-year-old man who was started on Carbamazepine for focal seizures 4 weeks ago presents with high daily fevers up to 39.0°C (102.2°F), a diffuse, pruritic, confluent morbilliform skin eruption covering 65% of his body surface area, and marked bilateral facial and periorbital edema. Laboratory evaluation reveals a white blood cell count of 16,500/mcL with 18% eosinophils (absolute eosinophil count 2,970/mcL) and atypical lymphocytes on peripheral smear. Serum ALT is 380 U/L (reference <40 U/L), AST is 310 U/L, and serum creatinine is 1.8 mg/dL (baseline 0.9 mg/dL). After stopping carbamazepine, what is the most appropriate next step in medical therapy?

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